BACKGROUND:This study explores hematological changes during trastuzumab deruxtecan (T-DXd) treatment in HER2-positive and HER2-low breast cancer patients, aiming to develop an efficacy prediction model for personalized clinical decisions. MATERIALS:A retrospective analysis of 114 patients treated with T-DXd at Beijing Chaoyang District Sanhuan Cancer Hospital (March 2023-December 2024) was conducted. Data included demographics, treatment history, and laboratory results. Efficacy was assessed via RECIST 1.1, with analyses using the Wilcoxon test and Kaplan-Meier method. RESULTS:HER2-positive patients had a progression-free survival (PFS) of 12.2 months vs. 10.2 months for HER2-low. Common adverse events included Nausea, primarily grade 1 or 2. T-DXd caused significant reductions in red blood cell count, hemoglobin, hematocrit, creatine kinase, and homocysteine (p < 0.05), along with increased red cell distribution width. Responders (CR+PR+SD) and progressors (PD) differed in platelets, plateletcrit, and homocysteine (p < 0.05). Stratification by estrogen receptor (ER) and progesterone receptor (PR) expression and Ki67 revealed distinct PFS outcomes. We aimed to predict the efficacy of T-DXd using pre-treatment hematological parameters and various machine learning models, including Random Forest, SVM, XGBoost, and LightGBM. The performance of the optimal models, as evaluated by leave-one-out cross-validation, yielded AUC values of 0.748 (XGBoost), 0.881 (SVM), and 0.830 (SVM) for models based on Complete Blood Count (CBC) parameters, biochemical markers, and their combination, respectively. CONCLUSION:Hematological toxicity is a recognized concern with T-DXd therapy. Our predictive model demonstrates strong performance in identifying patients suitable for treatment, highlighting that rigorous monitoring of hematological indicators is critical for mitigating risk and upholding safety standards in clinical practice.

Upper limb dysfunction remains a frequent challenge for breast cancer survivors following modified radical mastectomy (MRM) with axillary lymph node dissection (ALND). Although alterations in scapular function may be relevant to postoperative shoulder impairment, scapular-region loading patterns and their relationships with upper limb function remain insufficiently understood. This exploratory cross-sectional study examined the associations between scapular-region pressure distribution and upper limb function during shoulder flexion in this population. Twenty-six female breast cancer survivors (mean age, 49.2 ± 11.0 years) who had undergone MRM with ALND and achieved at least 120° of active shoulder flexion were included in this cross-sectional study. A body pressure sensor system recorded scapular-region pressure distribution bilaterally at 0°, 30°, 60°, 90°, and 120° of shoulder flexion under standardized supine conditions. Key variables included the maximum pressure value (MPV), number of peak pressure values (NPPV), and the horizontal distance of the MPV from the center of pressure (HDSMC). Shoulder range of motion, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and scapular positioning were also assessed. Side-to-side differences in scapular-region pressure distribution and scapular position were observed. In separate stepwise regression analyses, active shoulder flexion was associated with the DASH score (adjusted R² = 0.190), DIASS at 90° of shoulder flexion (adjusted R² = 0.186), NPPV at 30° (adjusted R² = 0.119), and HDSMC at 90° (adjusted R² = 0.206). However, the association with NPPV30° was not statistically significant in a Spearman sensitivity analysis. Simple linear regression analysis showed that the surgical-to-non-surgical side ratio of MPV at 120° of shoulder flexion was associated with the DASH score (adjusted R² = 0.245). Altered and asymmetric scapular-region pressure-distribution patterns were associated with shoulder mobility and self-reported upper limb disability in this exploratory sample of breast cancer survivors following MRM with ALND. Given the small sample size, cross-sectional design, absence of a healthy control group, and lack of direct measurements of scapular kinematics, these findings should be considered preliminary. Larger prospective controlled studies are needed to validate these pressure-derived measures and determine their clinical relevance.

3034 Background: SG and T-DXd are both antibody-drug conjugates (ADC) approved in China for HER2- MBC patients. However, direct real-world comparisons between these two therapies in HER2- MBC patients in China remain limited. This study aimed to evaluate and compare clinical outcomes of SG and T-DXd in Chinese patients with HER2- MBC in real-world practice. Methods: This retrospective study included 306 HER2- MBC patients, with 151 treated with SG and 155 treated with T-DXd. Separate propensity score matching (PSM) was performed for the triple-negative (TN) and hormone receptor-positive (HoR+) cohorts, respectively. Matching variables for both cohorts included age, HER2 expression, prior ADC use, number and site of metastases (liver, brain), and prior lines of therapy. For TN cohort only, DFI, prior taxane and PD-1/PD-L1 inhibitor use were additionally matched (caliper = 0.1). Clinical outcomes included real-world progression-free survival (rwPFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Median follow-up was 13.4 mo (SG-TN), 12.0 mo (SG-HoR+), 12.4 mo (T-DXd-TN), and 12.0 mo (T-DXd-HoR+). After PSM, 33 TN patients and 28 HoR+HER2- patients were matched in each treatment group. Baseline clinical characteristics were well-balanced. In TN patients, rwPFS was comparable between SG and T-DXd (5.0 vs 5.7 mo, HR=0.63, P =0.138). The comparable effectiveness of SG and T-DXd was also observed in both HER2-null ( P =0.498) and HER2-low ( P =0.250) subgroup. Meanwhile, SG showed a trend toward improved rwOS (NR vs 13.1 mo, HR=1.75, P =0.216). However, T-DXd demonstrated significantly higher ORR (18.2% vs 45.5%, P =0.017) and DCR (45.5% vs 75.8%, P =0.012) compared to SG. In HoR+HER2- patients, T-DXd showed significantly longer rwPFS compared to SG (9.8 vs 5.5 mo, HR=0.41, P =0.010), especially among those with HER2-low disease (8.4 vs 5.3 mo, HR=0.36, P =0.007); OS data were immature. ORR (14.3% vs 39.3%, P =0.035) and DCR (42.9% vs 85.7%, P <0.001) favored T-DXd, as well. Subgroup analyses indicated that T-DXd in those with DFI >12 months prolonged rwPFS than SG (10.2 vs 3.5 mo, HR=0.46, P =0.036). In HoR+ patients, the median rwPFS was significantly longer in T-DXd group than SG group in the majority of subgroups. Conclusions: In this real-world PSM analysis, T-DXd showed improved rwPFS compared with SG in HoR+HER2- MBC patients, while both regimens had generally comparable effectiveness in TN patients. These findings suggest that treatment selection may be influenced by hormone receptor status and the duration of DFI. Further prospective studies are warranted to validate these observations.

Despite the established benefit of adjuvant trastuzumab emtansine (T-DM1) over trastuzumab in HER2-positive early breast cancer (eBC) with residual disease after neoadjuvant chemotherapy plus HER2-targeted therapy, comparison of efficacy between T-DM1 and dual HER2 blockade (trastuzumab plus pertuzumab, HP) remains undetermined. This study evaluates survival outcomes with adjuvant T-DM1 versus HP in a multicenter real-world cohort. Breast cancer patients with residual disease after neoadjuvant treatment from 3 centers in China who received either T-DM1 or HP from 2018 to 2024 were included. To analyze treatment effects, multivariable Cox regression was utilized as the primary analysis, with sensitivity analyses employing Firth’s penalized method, inverse probability of treatment weighting (IPTW), and propensity score matching (PSM) in the anthracycline (AC)-naïve cohort (N = 212). Totally 230 patients were enrolled. Among them, 203 received TCbHP, 9 received THP, and 18 received AC-containing chemotherapy plus HP before surgery. In the AC-naïve cohort, 89 had T-DM1 as adjuvant treatment and 123 had HP instead. More iDFS events were observed in HP group than T-DM1 group (19 vs. 2 events respectively). Multivariable Cox regression demonstrated superior iDFS with T-DM1 compared with HP (2-year iDFS: 97.6

Background: Sacituzumab govitecan (SG), an anti-Trop-2 antibody-drug conjugate (ADC), was approved for metastatic triple-negative breast cancer (mTNBC) with ⩾1 prior therapy and hormone receptor-positive (HoR+) breast cancer progressing on cyclin-dependent kinase 4/6 inhibitor and chemotherapy. However, little real-world evidence is available in China, and the potential predictive biomarker of SG has not been fully investigated. Objectives: Our study aimed to evaluate the effectiveness, safety, and biomarker of SG in Chinese metastatic breast cancer (MBC) patients. Design: A total of 165 MBC patients treated with SG between June 2023 and December 2024 in 4 institutions nationwide were included in this study. SG was administered intravenously at a dosage of 10 mg/kg on days 1 and 8 of a 21-day treatment cycle. Methods: Demographic and clinical data were retrospectively collected and analyzed. Clinical outcomes included real-world progression-free survival (rwPFS), overall survival (OS), objective response rate (ORR), disease control rate, and toxicity. Results: In 103 mTNBC patients, median rwPFS was 5.1 months (95% confidence interval (CI): 3.8–7.4) and median rwOS was 19.7 months (95% CI: 17.3–not reached); in 62 HoR+HER2− patients, median rwPFS was 5.8 months (95% CI: 4.7–7.9), and OS data were immature. Prior PD-1/PD-L1 inhibitors exposure in TNBC showed significantly shorter rwPFS ( p = 0.025) in multivariate analysis. Longer rwPFS was observed in patients receiving SG as front line (line 1–2) compared to later line (line ⩾3) in both populations. mTNBC patients harboring PIK3CA mutation were associated with reduced PFS of SG ( p = 0.034). No new safety signal was observed in this study. Conclusion: In conclusion, SG showed similar effectiveness with ASCENT and TROPiCS-02 study in heavily pretreated Chinese MBC patients. Given the compromised effectiveness in patients with prior PD-1/PD-L1 inhibitors or PIK3CA mutation, future investigations are warranted to explore SG-based combination regimens or novel therapeutic strategies in the above population.

Background: Everolimus (EVE) has been approved by the FDA for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer patients. However, in clinical practice, the toxicity of the standard dose (10 mg/d) limits its use. Method: This study aimed to compare the efficacy, safety, and compliance of 5 mg/d and 10 mg/d EVE in combination with endocrine therapy in btreast cancer patients. Results: Compared with the 5 mg/d group, the 10 mg/d group included more primary endocrine-resistant patients (46.7 % vs. 24.6 %; P = 0.036). There was no significant difference in overall ORR and DCR between the two groups and the difference in median PFS and OS was not statistically significant (PFS: 7.07 m vs. 8.07 m, P = 0.663; OS: 29.47 m vs. 30.53 m, P = 0.615). In the subgroup of patients with primary endocrine resistance and premenopausal patients, the PFS benefit of the 10 mg/d group was more significant. In the safety analysis, the 5 mg/d group had lower rates of fatigue (29.2 % vs. 53.3 %; P = 0.038) and diarrhea (10.8 % vs. 33.3 %; P = 0.011). In the compliance analysis, the 5 mg/d group had a lower treatment interruption rate, and fewer patients stopped treatment due to adverse reactions. For most patients, 5 mg/d and 10 mg/d EVE combined with endocrine therapy showed comparable efficacy, but the safety and compliance of 5 mg/d were better. Conclusions: For patients with primary endocrine resistance and premenopausal patients, using standard-dose EVE resulted in greater PFS benefit. (c) 2025 Asian Surgical Association and Taiwan Society of Coloproctology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

•Trastuzumab deruxtecan showed superior intracranial overall response rate (ORR) and median progression-free survival (mPFS) than controls in both stable and active brain metastases.•DEBBRAH, TUXEDO-1, and DESTINY-Breast 12 confirm durable intracranial activity in brain metastases with trastuzumab deruxtecan.•Real-world ROSET-BM data reported median overall survival (OS, 27.0 months) and mPFS (14.6 months) in active BM, reinforcing T-DXd efficacy.•In leptomeningeal metastases (LM) cohorts, T-DXd achieved clinical benefit rate (71.4-100%), mOS (10.4-13.3 months), and mPFS (8.9-17.5 months) across studies.•For active BM, local intervention plus T-DXd (or tucatinib combination) is recommended based on efficacy stratification.

Objective:A subset of patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer shows insensitivity to neoadjuvant therapy (NAT), often evidenced by imaging results indicating stable disease (SD) or progressive disease (PD), which may reflect intrinsic resistance to treatment. We aimed to investigate the factors associated with NAT insensitivity and its prognostic value in HER2+ breast cancer. Methods:This study included consecutive patients with HER2+ breast cancer who received NAT consisting of chemotherapy combined with anti-HER2 monoclonal antibodies. NAT insensitivity was defined as SD or PD on the basis of treatment response evaluations. Statistical analyses were conducted on the collected clinical data, and HER2 heterogeneity was subsequently assessed. Results:A total of 541 patients were included in the study, among whom 63 (11.6%) were categorized as NAT-insensitive group and 478 (88.4%) as NAT-sensitive group. Hormone receptor (HR) status (P=0.033), HER2 status (P=0.036) and anti-HER2 therapy (P=0.007) were associated with NAT sensitivity. NAT-insensitive group had a significantly shorter event-free survival (EFS) (3-year: 69.4% vs. 94.3%; P<0.001) and remained an independent prognostic factor according to Cox models [hazard ratio (HR)=8.637; 95% confidence interval (95% CI), 3.091-24.136; P<0.001]. Exploratory analysis revealed a greater proportion of HER2 heterogeneity in the NAT-insensitive group (19.4% vs. 4.3%; P=0.035). Conclusions:HR positivity, HER2 2+/fluorescence in situ hybridization (FISH)+ status, and trastuzumab monotherapy are associated with NAT insensitivity, and NAT insensitivity independently indicates poor EFS. This study also highlights the need for prospective studies to clarify the role of HER2 heterogeneity and other mechanisms involved in predicting the response to NAT.

e13181 Background: SG was approved to treat patients who have received ≥1 prior systemic therapy in metastatic setting with triple-negative (TN) MBC or prior endocrine therapy including CDK4/6 inhibitor and chemotherapy with hormone receptor-positive (HoR+) MBC. Little real-world evidence is available in China. This study aimed to describe treatment patterns, clinical outcomes and safety profile for SG-based therapy and explore the predictors of effectiveness in Chinese women with MBC in real-world practice. Methods: MBC patients treated with SG (10 mg/kg D1, D8, every 21 days) between June 2023 and December 2024 in 3 institutions nationwide were included in this study. Clinical outcomes included real-world progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and clinical benefit rate (CBR). Adverse event (AE) was evaluated according to the NCI-CTC version 5.0. Results: A total of 165 patients were enrolled, with 103 (62.4%) TN and 62 (37.6%) HoR+HER2-. Among TNBC and HoR+HER2- patients, median age was 51 and 58 years, 10.7% and 12.7% ECOG scores of 2, 72.8% and 85.5% of patients with visceral metastases, 13.6% and 16.1% of patients with brain metastasis, median prior lines in metastatic setting were 2 and 3, respectively. The majority of patients were treated with SG monotherapy, and a small number received SG-based combination therapy. At the cutoff date of 21 Jan 2025, in TNBC patients, median rwPFS was 5.1 mo (95%CI 3.8-7.4), median rwOS was 19.7 mo (95%CI 17.3-NR), ORR was 17.5% and DCR was 47.6%; in HoR+HER2- patients, median rwPFS was 5.8 mo (95%CI 4.7-7.9), the OS data were immature, ORR was 9.7% and DCR was 40.3%. Prior PD-1/PD-L1 inhibitors exposure (3.6 vs 7.8 mo, HR = 1.91, P = 0.025) and liver metastasis (5.5 vs 7.9 mo, HR = 2.96, P = 0.021) showed significantly shorter rwPFS in TNBC and HoR+HER2- patients in multivariate analysis, respectively. Longer rwPFS was observed in patients receiving SG as front line (line 1-2) compared to those as later line (line ≥3) both in TNBC ( P = 0.017) and HoR+HER2- patients ( P = 0.652). SG-based combination therapy showed a trend to improved PFS compared to monotherapy both in TNBC (14.2 vs 4.6 mo, HR = 0.51, P = 0.115) and HoR+HER2- patients (11.3 vs 5.8 mo, HR = 0.35, P = 0.159). Brain metastasis and prior use of ADCs did not impact the effectiveness of SG. Incidence of AEs of any grade was 52.7% and grade ≥3 AEs was 20.0%. No new safety signal was observed in this study. 14 (8.5%) patients discontinued the treatment and 15 (9.1%) had dose reduction due to AEs. Conclusions: In the real-world practice, SG showed anti-tumor activity in heavily pretreated Chinese MBC patients, consistent with existing clinical trials. mTNBC patients with no prior PD-1/PD-L1 exposure had longer rwPFS. Promising PFS of SG-based combination therapy encourages randomized controlled trials in the future. Clinical trial information: NCT06356519 .

Breast cancer (BC) is the most common malignancy in women, yet the dynamics of the intratumoural microbiome during tumour initiation, progression, and treatment remain poorly understood. Prior studies are predominantly cross-sectional and limited by indirect microbial inference from RNA-seq data. This study presents a comprehensive analysis of intratumoural microbiota across breast tissue samples by high-depth 16S rRNA sequencing (11 W tags), featuring two longitudinally paired cohorts for dynamic microbial profiling during tumour progression and treatment. Samples included 165 benign nodules (82 non-transforming, 83 that later progressed to cancer with matched malignant tissues); 180 primary BC tissues and 165 benign controls; and 101 neoadjuvant therapy (NAT) specimens (15 pCR, 86 non-pCR, with paired pre/post-treatment samples). We identified a cluster of taxa (Aeromicrobium, Halomonas, Dietzia, Nesterenkonia, Delftia, Nitriliruptor) depleted in nodules undergoing malignant transformation, declining with disease progression and partially restored after NAT, with transient enrichment early in transformation. Opposing trends were observed for Paenibacillus and Methyloversatilis . These changes corresponded to shifts in amino acid, lipid, and glycan metabolism. FISH and TEM analyses identified Paenibacillus pasadenensis and Halomonas hamiltonii within tumour cells, with opposing effects on tumour proliferation and activation. In addition, we developed two predictive models with high clinical relevance: one stratifying malignancy risk in nodules, and another predicting NAT response, both of which achieved strong performance in external validation. This longitudinal characterisations of intratumoural microbiota during breast tumourigenesis and treatment offer novel insights for precision oncology and microbiome-based interventions in breast cancer.

Background: The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is widely utilized as the first-line treatment for hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients. However, there has been long debates on the choice between CDK4/6i plus ET and chemotherapy (CT), especially those with visceral metastasis or visceral crisis. Several prospective trials suggested a suspected superiority of CDK4/6i over CT, however, conclusions vary among different studies due to the complexity of treatment lines and different inclusion criteria. Here we report CDK4/6i plus ET versus CT in first line treatment of HR+/HER2- MBC in a real-world setting. Methods: The medical records of patients diagnosed with HR+/HER2- MBC from 2020 to 2023 in 6 institutions were retrospectively evaluated. And patients received first-line CDK4/6i plus ET or first-line CT were included in this study. Results: A total of 339 patients were available for analysis. 244 (72%) patients received CDK4/6i plus ET and 95 (28%) patients received CT. The median PFS of CDK4/6i plus ET cohort was significantly superior to CT group (17.2 months versus 9.1 months, hazard ratio = 0.49; 95% CI, 0.36 to 0.66; P < 0.0001). Subgroup analysis showed similar results, except subgroup of patients with visceral crisis (hazard ratio =0.73; 95% CI, 0.37 to 1.43; P = 0.36) or primary endocrine resistance (hazard ratio =0.59; 95% CI, 0.33 to 1.06; P = 0.08). The median overall survival was not reached. No significant difference of grade 3 or worse adverse events was observed in two groups (25.8% vs 26.3%, P = 0.93). Conclusions: In a real-world setting, first line CDK4/6i plus ET showed better efficacy than chemotherapy in patients with HR+/HER2- MBC, while CT and ET showed similar results in patients with visceral crisis or primary endocrine resistance. Safety profile was similar between two groups. This study provides real-world data for future clinical decision. Citation Format: Biyun Wang, Yifan Chen, Yizhao Xie, Yuan Peng, Ning Xie, Die Sang, Xinhua Han, Yanxia Zhao, Juanjuan Li. First line CDK4/6 inhibitors plus endocrine therapy versus chemotherapy for HR+/HER2- metastatic breast cancer patients in real world: a multicenter YOUNGBC-30 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-07-16.

Objective To evaluate the efficacy and safety of rivaroxaban in preventing catheter-related thrombosis (CRT) in breast cancer patients undergoing chemotherapy with peripherally inserted central catheters (PICC). Methods A prospective cohort study enrolled breast cancer patients who underwent PICC placement for chemotherapy at the San Huan Cancer Hospital from November 2021 to August 2023. The treatment group received 10 mg of oral rivaroxaban daily for 2 months along with routine grip strength training, while the control group received grip strength training only. CRT occurrence was confirmed by vascular ultrasound, and group comparisons were made using the χ2 test, with logistic regression analyzing CRT risk factors. Results Of 314 patients, 181 received treatment and 133 were in the control group. The treatment group had a significantly lower incidence of CRT (2.2%, 4/181) compared to the control group (12.0%, 16/133) (p <0.001). Univariate analysis showed a higher risk of CRT in patients in the non-prophylaxis group (p = 0.002), patients aged ≥50 years (p = 0.014), and those with prior endocrine therapy (p = 0.030). Multivariate analysis identified rivaroxaban prophylaxis (p = 0.009) and age (p = 0.026) as independent risk factors for thrombosis. The use of rivaroxaban for prophylactic anticoagulation was safe. All CRT-diagnosed patients completed their antitumor therapy without new thrombosis or pulmonary embolism. Conclusion Two months of rivaroxaban prophylaxis effectively and safely reduce CRT incidence in breast cancer patients with PICC.

Anaplastic thyroid carcinoma (ATC) is one rare type of thyroid carcinoma without standard systemic treatment for advanced disease. Recent evidence has demonstrated promising efficacy of immune checkpoint inhibitors, particularly those targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), in a variety of solid tumors. However, there have been no research of immune checkpoint inhibitors plus chemotherapy in ATC. Here, we present the case of a 37-year-old man with metastatic ATC with positive PD-L1 expression, who achieved long-term remission of 34 months after later-line treatment with zimberelimab (a PD-1 inhibitor) and nab-paclitaxel, followed by single-agent zimberelimab maintenance therapy. After three cycles of the combination treatment, the thyroid lesion and the liver metastases shrank dramatically, leading to the best overall response of partial remission. PD-L1 expression may serve as a potential biomarker for tumor response to immune checkpoint inhibitors in ATC. Our review highlights the need for further studies investigating the role of PD-L1 status as biomarker to predict the prognosis of immunotherapy in the treatment of ATC.

Background Anthracyclines are fundamental in the chemotherapy treatment of breast cancer,but these treatments often lead to changes in physique,such as increased body fat and decreased cardiopulmonary function,alongside gastrointestinal reactions and bone marrow suppression,thereby impacting the patients' quality of life. Current studies on the ameliorative effects of exercise on these side effects yield inconsistent results,necessitating further research. Clinically,the efficacy and safety of exercise prescriptions in mitigating these chemotherapy side effects in breast cancer patients warrant further exploration. Objective This study aims to investigate the effectiveness and safety of aerobic exercise in improving the physique and quality of life of breast cancer patients during anthracycline-based chemotherapy. Methods This study is a randomized controlled trial involving 44 adult female breast cancer patients who received anthracycline-based chemotherapy at Beijing Chaoyang Sanhuan Cancer Hospital,from March 2022 to January 2023. They were randomly assigned to an exercise group(23 participants)and a control group(21 participants). The control group was informed about personalized exercise guidance after chemotherapy. The exercise group,under the supervision of rehabilitation therapists,engaged in workouts during their hospital stay and continued personalized exercise interventions at home with self-monitoring and remote supervision by researchers. Key outcome measures,including physique and quality of life,were collected before and after chemotherapy,along with the incidence and severity of gastrointestinal reactions,bone marrow suppression,and exercise-related adverse events. Covariance analysis,using pre-chemotherapy data as covariates,compared the physique and quality of life between the two groups. Results Four participants were lost during the intervention and follow-up,leaving 40 participants(21 in the exercise group,19 in the control group). No severe adverse events were observed during the exercise intervention. The average compliance with the exercise intervention was 81.8％;average compliance per exercise session was 91.9％,and average compliance with exercise intensity was 92.5％. Post-chemotherapy,the exercise group showed lower body fat weight,body fat percentage,visceral fat area,waist circumference,waist-to-hip ratio,and significantly higher grip strength of the dominant hand and relative peak oxygen uptake(VO2peak)compared to the control group(P<0.05). The incidence of functional impairments post-chemotherapy in the exercise group(7/20)was significantly lower than in the control group(12/16)(x2=5.707,P=0.017). Post-chemotherapy,the exercise group reported significantly lower scores in physical condition,emotional condition,and additional scores,and higher functional condition scores than the control group(P<0.05). Post-chemotherapy,the control group's physical condition scores(P<0.001)and the exercise group's functional condition scores(P=0.017)were higher than pre-chemotherapy. The control and exercise groups underwent 84 and 94 anthracycline chemotherapy sessions,respectively,with the control group experiencing 84 gastrointestinal reactions and 71 bone marrow suppressions,and the exercise group experiencing 54 gastrointestinal reactions and 45 bone marrow suppressions,showing statistically significant differences between the groups(P<0.05). Conclusion Aerobic exercise during anthracycline chemotherapy can improve the physique and quality of life of breast cancer patients and is safe when supervised.

Objective:Limited real-world efficacy and safety data exist regarding the use of trastuzumab deruxtecan (T-DXd) in the Chinese population with human epidermal growth factor receptor (HER2)-positive and HER2-low advanced breast cancer (BC). This multicenter, observational, real-world study aimed to evaluate the efficacy and safety of T-DXd for the treatment of Chinese patients with HER2-positive and HER2-low advanced BC. Methods:The medical records of 61 patients were collected from The Second Hospital of Dalian Medical University, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing Jingxin Hospital, and Cancer Hospital of the Chinese Academy of Medical Sciences. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), and safety. PFS and OS were analyzed using the Kaplan-Meier method and log-rank test. Results:The primary endpoint, PFS was 10.51 months (95% confidence interval (CI), 3.02-NE) in the HER2-low group and 10.18 months (95% CI, 3.88-NE) in the HER2-positive group. Regarding the secondary endpoints in the HER2-low and HER2-positive groups, OS data were immature, ORR rates were 37.93% and 62.50%, DCR rates were 79.31% and 87.50%, and the median TTR rates were 1.28 and 1.31 months, respectively. In the subgroup analysis, front-line treatment with T-DXd was associated with increased beneficial effects. The primary adverse events (AEs) related to T-DXd treatment were gastrointestinal reactions and bone marrow suppression, which were predominantly grades 1-2, with no severe grade 4/5 AEs reported, only one patient developed infectious pneumonia. Conclusion:This study was the first multicenter, real-world study of T-DXd for advanced BC in China. The findings demonstrated that T-DXd may be an effective antitumor treatment with controllable adverse reactions in patients with advanced BC irrespective of HER2 expression levels.

Background Breast cancer-related lymphoma (BCRL) develops in 25% of breast cancer patients following treatment. It is a chronic condition where swelling persists despite interventions like compression hosiery and manual lymphatic drainage. Aim This study aimed to determine factors associated with early-stage lymphedema in women with breast cancer, investigate the relationship between lymphedema, lymphatic flow velocity, and body composition, and explore potential mechanisms for preventing BCRL. Design: Cross-sectional study. Setting: Inpatient rehabilitation unit Population: Thirty-four female patients with confirmed BCRL (age: 49.6 ± 8.7 years; height: 158.6 ± 4.1 cm; weight: 60.2 ± 9.8 kg) and 26 healthy controls (age: 50.5 ± 15.1 years; height: 160.9 ± 5.9 cm; weight: 62.9 ± 10.1 kg) were enrolled between 2024 and 2025. Methods Lymphatic duct diameter and flow velocity at the right venous angle were measured using ultrasound. Hand grip strength was assessed using a dynamometer, and body composition was analyzed using a bioimpedance analyzer (InBody 770; InBody Co., Seoul, Korea). Statistical analyses included paired t-tests to compare BCRL and control groups and Spearman's correlation for associations between clinical characteristics. Receiver operating characteristic analysis was used to determine diagnostic thresholds for BCRL. Results Compared to healthy controls, the BCRL group showed significantly higher lymphatic flow velocity, lower phase angle, and reduced grip strength (all p < 0.01). Age was positively correlated with extracellular water (ECW) but negatively with phase angle, while grip strength was positively correlated with phase angle. The optimal diagnostic cutoffs for lymphedema were: lymphatic flow velocity ≥ 7.7 cm/s (35.3% sensitivity, 96.2% specificity), phase angle ≤ 4.05° (92.3% sensitivity, 70.6% specificity), and grip strength ≤ 18.1 N (88.5% sensitivity, 67.6% specificity). Conclusion Increased lymphatic flow velocity, decreased phase angle, and reduced grip strength were significant early-stage indicators of BCRL. Clinical rehabilitation impact: Identifying early risk factors for lymphedema can help clinicians understand its mechanism and enable timely interventions to prevent its progression.

Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved in China for HER2-positive or HER2-low metastatic breast cancer (MBC) patients. Little real-world evidence is available in China. This study aimed to investigate the real-world effectiveness and safety of T-DXd in Chinese MBC patients. Methods: This study retrospectively enrolled 309 MBC patients treated with T-DXd across 9 institutions nationwide in China between December 2019 and March 2024. T-DXd was administered intravenously at a dose of 5.4 mg/kg on day 1 of a 21-day cycle. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Real-world adverse events (AEs) were graded according to CTCAE 4.0. The study was registered at ClinicalTrials.gov (NCT05594082). Findings: A total of 309 MBC patients were included, with 168 HER2-positive and 141 HER2-negative patients (133 of HER2-low and 8 of HER2 0). Among HER2-positive and HER2-negative patients, median age was 53.5 and 55.0 years, 14.3% and 17.7% ECOG scores of 2, 83.9% and 84.4% patients with visceral metastases, 32.7% and 23.4% patients with brain metastasis, respectively. The median number of lines of therapy (LOT) for MBC patients receiving T-DXd was 4 for both groups. At the cutoff date of 30 July 2024, in patients with HER2-positive MBC, median rwPFS and OS was 12.1 [95% confidence interval (CI): 8.5-14.7] and 22.7 months (95% CI: 16.6-28.8). The longer rwPFS, median 23.3 months, was observed in LOT 1-2, than 12.2 months in LOT 3-5 and 8.2 months in LOT≥6 (P=0.001). In patients with HER2-negative MBC, median rwPFS and OS was 7.7 (95% CI: 6.6-8.8) and 15.7 months (95% CI: 11.4-20.0). The median rwPFS for HR+ and HR- patients was 7.7 and 8.1 months, respectively (P=0.870). Longer rwPFS of 9.5 months was observed in LOT 1-4 compared to 6.4 months in LOT≥6 among HER2-negative patients (P=0.026). Patients with prior ADCs exposure showed significantly shorter rwPFS of T-DXd in both HER2-positive (P=0.032) and negative patients (P=0.039). Brain metastasis did not impact the effectiveness of T-DXd. Incidence of AEs of any grade was 69.3% and severe (grade 3 or above) AEs was 13.9%; no fatal AEs were observed. Interstitial lung disease (ILD) occurred in 23 patients (7.4%), with 15 (4.9%) of grade 1, 4 (1.3%) of grade 2, and 4 (1.3%) of grade 3. 80.7% of ILD patients, including all with grade 1 and one with grade 2, underwent a rechallenge with T-DXd after symptomatic treatments and careful evaluations. Interpretation: In this largest dataset of T-DXd for Chinese patients with MBC to date, encouraging rwPFS of T-DXd was seen in heavily pretreated HER2-positive and HER2-negative MBC patients. Longer rwPFS was observed in MBC patients with fewer LOT and no prior ADC exposure. Meanwhile, T-DXd showed a manageable toxicity profile in understudied real-world patients. Rechallenge of T-DXd is feasible following effective symptomatic treatments and comprehensive assessments of ILD severity and recovery. Funding: This work was supported by grants from Beijing Science and Technology Innovation Medical Development Foundation (KC2022-ZZ-0091-4).

Purpose Anthracyclines have been one of the standard therapies for breast cancer (BC), and dose-related cardiotoxicity is one serious side effect. Exercise is an effective strategy for the prevention and management of BC, endorsed by experts in both exercise and oncology. However, there is a great deal of confusion about the effectiveness of exercise on anthracycline-induced cardiotoxicity and the exercise prescription (i.e., timing, type, and intensity) for cardiotoxicity, which limits its application in clinical settings. The aim of this article is to review the safety of exercise in BC patients receiving anthracyclines and its effectiveness in preventing cardiotoxicity. Methods Six electronic databases were searched using terms related to exercise, BC, anthracyclines, and cardiotoxicity for retrieving clinical randomized controlled trials in either Chinese or English. A summary of the included literature was also provided. Results Of 202 records screened, 10 were eligible. A total of 434 BC patients (stage I–IIIC, mean age ranged from 43.5 to 52.4 years) were included. The main findings were that: (1) Acute (a single bout) moderate-to-vigorous aerobic exercise could prevent NT-proBNP elevation beyond the threshold of acute myocardial injury; (2) Long-term (> 8 weeks) moderate-to-high intensity aerobic exercise (continuous or interval) could improve or maintain left ventricular ejection fraction and cardiorespiratory fitness in BC patients. However, the optimal timing, type, and intensity of exercise for people with BC to prevent cardiotoxicity remain unclear. Conclusion Moderate-to-vigorous intensity exercise may be an effective non-pharmacological approach to mitigate cardiotoxicities induced by anthracyclines in women with BC. However, the optimal exercise prescription for preventing cardiotoxicity remains unclear.

IntroductionAn increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD.MethodsHere, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD.ResultsWe found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70.DiscussionOur study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage.